Chemotherapy is an important part of treatment for children with cancer. This form of treatment has proven successful and on average three out of four children are cured. But an adverse consequence of these treatments is that not only are cancer cells destroyed, but DNA in healthy tissues can also be damaged. In some children, this happens in the brain.
The team examined the effect of eating less in mice with different levels of Ercc1 deficiency. 'Half of the mice received 30% less of the normal amount of food. Water was available without restriction. We then counted the number of remaining Purkinje cells at different ages. Depending on the Ercc1 level, we saw 25 to 40% more Purkinje cells in mice that ate less. We therefore conclude that dietary restriction in these mice protects against cell death from DNA damage, possibly also from chemotherapy. And thus that fasting reduces brain damage. These are hopeful but early results. Before we know whether fasting also has a protective effect on the brain in children with cancer, further clinical studies are needed.'
There are similarities between DNA damage to brain cells caused by chemotherapy and diseases of aging in the brain, such as dementia and Parkinson's disease. The results from this study therefore offer new leads for these diseases. Vermeij: 'Through publications and collaborations, we share our knowledge with specialists outside the Máxima. For example, we are part of the network of Dutch neuroscientists called MODEM (Mechanisms Of DEMentia) and the European consortium TC-NER, which is researching congenital syndromes in children with a similar DNA repair defect. It's great how in this way we manage to make scientific progress not only for children with cancer, but also for these other groups of patients.'
First lead
Previous research by senior postdoc and Oncode researcher Dr. Wilbert Vermeij showed that eating less, or dietary restriction, has a positive effect on nervous system health in mice lacking the so-called Ercc1 gene. Vermeij: 'From previous fundamental research by our group, we knew that Ercc1 plays an important role in the repair of DNA damage. When there is an error in the Ercc1 gene, DNA remains damaged. This damage resembles the damage that can occur after chemotherapy, resulting in faster cell aging and worse brain function.' Currently, there is no treatment to prevent or cure this type of brain damage. 'To find a treatment, we bred a mouse in which the Ercc1 gene stopped working properly. We found that eating less in this type of mouse has an extraordinarily positive effect on the health of the nervous system, of which the brain is also a part.'Counting and comparing
Following this result, PhD student María Bjork Birkisdóttir together with Vermeij and Dr. Dick Jaarsma of the Rotterdam Erasmus Medical Center investigated the role of eating less on the protection of Purkinje brain cells. The results of this research were published in the journal Frontiers in Aging Neuroscience. Says Birkisdóttir, 'We specifically introduced the flaw in Ercc1 into the Purkinje cells, allowing damage to accumulate only there and allowing us to properly investigate the effect of dietary restriction.'The team examined the effect of eating less in mice with different levels of Ercc1 deficiency. 'Half of the mice received 30% less of the normal amount of food. Water was available without restriction. We then counted the number of remaining Purkinje cells at different ages. Depending on the Ercc1 level, we saw 25 to 40% more Purkinje cells in mice that ate less. We therefore conclude that dietary restriction in these mice protects against cell death from DNA damage, possibly also from chemotherapy. And thus that fasting reduces brain damage. These are hopeful but early results. Before we know whether fasting also has a protective effect on the brain in children with cancer, further clinical studies are needed.'